The proposed research includes the following objectives and methods: (1) to gain a general understanding of the biochemical and genetic mechanisms controlling the synthesis, repair and recombination of DNA, (2) to establish the functions of genes that are essential for the continuation of DNA replication after it is intiated, (3) to elucidate the role of phage and host functions in the mechanism by which the monomer DNA of the early T4 replicative stage is converted into the concatemer DNA of the later replicative stage, (4) to shed light on the mechanism by which hydroxyurea and its derivatives inhibit the conversion of ribonucleotide into the corresponding deoxyribonucleotides, (5) to comparatively study the control of deoxyribonucleotide biosynthesis in normal mammalian cells and their chemically transformed, tumorigenic counterparts, (6) to carry out both physical and biochemical characterization of intracellular DNA from mutants defective in DNA synthesis, (7) to isolate by a simple and specific method both temperature-sensitive and amber DNA arrested synthesis mutants.